Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer
Knocking down the UBC12 with siRNA could significantly suppress the Neddylation pathway and result in an admirable anti-cancer effect. However, how to transport siRNA in vivo with low potential toxicity is an urgent problem to be solved. For enhancing bioavailability of siRNA, folic acid (FA)-modifi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S026412752100201X |
| _version_ | 1819086328359288832 |
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| author | Zhanxia Zhang Yongqing Heng Wei Cheng Yongfu Pan Shuaishuai Ni Hegen Li |
| author_facet | Zhanxia Zhang Yongqing Heng Wei Cheng Yongfu Pan Shuaishuai Ni Hegen Li |
| author_sort | Zhanxia Zhang |
| collection | DOAJ |
| description | Knocking down the UBC12 with siRNA could significantly suppress the Neddylation pathway and result in an admirable anti-cancer effect. However, how to transport siRNA in vivo with low potential toxicity is an urgent problem to be solved. For enhancing bioavailability of siRNA, folic acid (FA)-modified PLGA (poly(lactic-co-glycolic acid))-TK (thioketal)-PEG (polyethylene glycol) nanomedicine was designed for siRNA delivery. The nano-vector possesses spherical morphology and admirable biocompatibility. After targeted endocytosis through the selective recognition between FA and its receptor in liver cancer cells, the genetic nanomedicine was triggered by high ROS level and released its cargo siRNA in tumor microenvironment. In vitro and In vivo results revealed that the genetic nanomedicine not only inhibits proliferation and promotes apoptosis of liver cancer cells, but also possesses excellent therapeutic efficacy by knowing down UBC12 and suppressing the Neddylation pathway as well as accumulating tumor-suppressive CRL substrates. Consequently, this work provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and smart response. Moreover, it inhibits the viability of liver cancer cells with high efficiency and low potential toxicity. Importantly, the PLGA nanomedicine demonstrates the encouraging potential for multifunctional nano-system applicable for cancer therapy. |
| first_indexed | 2024-12-21T21:18:30Z |
| format | Article |
| id | doaj.art-cce335ca75d843e69efec35b1acf1bc9 |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-12-21T21:18:30Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-cce335ca75d843e69efec35b1acf1bc92022-12-21T18:49:56ZengElsevierMaterials & Design0264-12752021-06-01204109648Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancerZhanxia Zhang0Yongqing Heng1Wei Cheng2Yongfu Pan3Shuaishuai Ni4Hegen Li5Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China; Corresponding author.Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, ChinaCancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, ChinaCancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, ChinaCancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, ChinaDepartment of Medical Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, ChinaKnocking down the UBC12 with siRNA could significantly suppress the Neddylation pathway and result in an admirable anti-cancer effect. However, how to transport siRNA in vivo with low potential toxicity is an urgent problem to be solved. For enhancing bioavailability of siRNA, folic acid (FA)-modified PLGA (poly(lactic-co-glycolic acid))-TK (thioketal)-PEG (polyethylene glycol) nanomedicine was designed for siRNA delivery. The nano-vector possesses spherical morphology and admirable biocompatibility. After targeted endocytosis through the selective recognition between FA and its receptor in liver cancer cells, the genetic nanomedicine was triggered by high ROS level and released its cargo siRNA in tumor microenvironment. In vitro and In vivo results revealed that the genetic nanomedicine not only inhibits proliferation and promotes apoptosis of liver cancer cells, but also possesses excellent therapeutic efficacy by knowing down UBC12 and suppressing the Neddylation pathway as well as accumulating tumor-suppressive CRL substrates. Consequently, this work provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and smart response. Moreover, it inhibits the viability of liver cancer cells with high efficiency and low potential toxicity. Importantly, the PLGA nanomedicine demonstrates the encouraging potential for multifunctional nano-system applicable for cancer therapy.http://www.sciencedirect.com/science/article/pii/S026412752100201XUBC12NeddylationsiRNA-loaded nanomedicineSmart responseTargeted delivery |
| spellingShingle | Zhanxia Zhang Yongqing Heng Wei Cheng Yongfu Pan Shuaishuai Ni Hegen Li Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer Materials & Design UBC12 Neddylation siRNA-loaded nanomedicine Smart response Targeted delivery |
| title | Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer |
| title_full | Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer |
| title_fullStr | Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer |
| title_full_unstemmed | Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer |
| title_short | Reactive oxygen species (ROS)-response nanomedicine through knocking down a novel therapeutic target NEDD8-conjugating enzyme UBC12 (UBE2M) in the treatment of liver cancer |
| title_sort | reactive oxygen species ros response nanomedicine through knocking down a novel therapeutic target nedd8 conjugating enzyme ubc12 ube2m in the treatment of liver cancer |
| topic | UBC12 Neddylation siRNA-loaded nanomedicine Smart response Targeted delivery |
| url | http://www.sciencedirect.com/science/article/pii/S026412752100201X |
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